The Oklahoma Medical Research Foundation proposes a Specialized Center of Research (SCOR) in systemic lupus erythematosus which will focus on understanding the roles of autoantibodies in SLE. The overarching goal of this center will be to integrate clinical rheumatic disease research with basic science investigators from throughout campus thereby strengthening basic science and patient oriented research in this state. Dr. Morris Reichlin is the Director, and he brings a distinguished career's worth of rheumatic disease research activities to this new integrated program. Briefly, this SCOR has five key investigators, five collaborating investigators (in-state), five collaborating investigators (out-of-state), nine additional arthritis investigators, fourteen basic science investigators, a Data and Analysis Core Director, Advisory Committee and a host of adjunct faculty, post-doctoral fellows, clinical fellows, MD-PhD students and graduate students. The key projects for this proposal include various approaches to understand how autoimmune responses start in SLE and how autoantibodies could lead to pathogenesis. The major projects in this SCOR will focus on understanding the development of autoantibodies with regards to symptom and SLE disease onset, exploring the role of autoantibodies in the development of dyslipidemias and accelerated cardiac disease, evaluating the basic role of B cell tolerance in the accrual of lupus autoantibodies, identifying potential etiologic triggers of these aberrant autoimmune responses and assessing the genetic predisposition to a severe serological and clinical SLE phenotype. A Data and Analysis Core and Administrative Core will support each of these individual projects. The primary Oklahoma SLE SCOR objectives are fourfold. First, this SCOR will strengthen research through integration of basic and clinical science in finding key etiological factors for SLE by supporting the above mentioned research projects. Second, biostatistical/research design issues will be incorporated into all ongoing rheumatic disease research in order to raise the current level of research activity. Third, key unique patient resources will be shared by several of the projects. Finally, this SCOR will provide a multidisciplinary structure and resources to strengthen current clinical rheumatic disease research through the influence of strong basic scientists involved in cardiovascular biology, lupus genetics, inflammation, coagulation, molecular biology, immunobiology, immunogenetics, clinical pharmacology and protein studies.